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At least 991 records · Page 55Linked to original sources
PubMed1999

Thiomenthol derivatives as novel percutaneous absorption enhancers.

Thiomenthol derivatives were synthesized and their promoting activity on the percutaneous absorption of ketoprofen from hydrogels was evaluated in rats. The apparent penetration rate (Rp) of ketoprofen absorbed from the hydrogel was estimated by the pharmacokinetic model derived under the assumption of a constant penetration rate through the skin after a lag time. As an index of promoting activity of thiomenthol derivatives, an enhancement factor (Ef) was defined as the ratio of the Rp value with enhancer to the value obtained with the control not containing enhancer. Skin irritancy evoked by these derivatives was investigated microscopically by using a cross-section of the excised skin onto which ketoprofen hydrogel was applied. Total irritation score (TIS) was estimated by summation of each irritation score in several parts of the skin. The physicochemical parameters of thiomenthol derivatives such as a partition coefficient (log P) and a steric energy were calculated and the quantitative relationships between these parameters and the Ef values or TIS values were investigated on the basis of multiple regression analysis. As a result, a parabolic relationship between log P and Ef was noted. A similar relationship was also observed in the case of TIS.

Administration, Cutaneous↗
PubMed1998

Na+-dependent Ca2+ extrusion governs response recovery in frog olfactory receptor cells.

To study the mechanism by which Ca2+, which enters during the odor response, is extruded during response recovery, recordings were made from isolated frog olfactory receptor cells using the suction pipette technique, while superfusing the olfactory cilia with solutions of modified ionic composition. When external Na+ was substituted with another cation, the response to odor was greatly prolonged. This prolongation of the response was similar irrespective of whether Na+ was replaced with Li+, which permeates the cyclic nucleotide-gated conductance, or choline, which does not. The prolonged current was greatly reduced by exposure to 300 microM niflumic acid, a blocker of the calcium-activated chloride channel, indicating that it is carried by this conductance, and abolished if Ca2+ was omitted from the external solution, demonstrating that Ca2+ influx is required for its generation. When the cilia were exposed to Na+-free solution after odor stimulation, the recovery of the response to a second stimulus from the adaptation induced by the first was greatly reduced. We conclude that a Na+-dependent Ca2+ extrusion mechanism is present in frog olfactory cilia and that it serves as the main mechanism that returns cytoplasmic Ca2+ concentration to basal levels after stimulation and mediates the normally rapid recovery of the odor response and the restoration of sensitivity after adaptation.

Adaptation, Physiological↗
PubMed2003

Effect of aromatics on lung mucociliary clearance in patients with chronic airways obstruction.

BACKGROUND: Complementary and alternative medicine have become an increasingly topical theme in respiratory medicine. Aromatics are a commonly used ingredient in a number of proprietary medicines. It is well established that lung mucus clearance is impaired in patients with chronic airways obstruction. This study investigated whether aromatics delivered by inunction could be objectively shown to enhance lung clearance. METHODS: We studied 12 patients with chronic bronchitic with a mean standard error (SE) age of 67 (2) years (mean [SE] tobacco consumption history of 64 [12] pack-years). We used a randomized, single-blinded, placebo-controlled crossover trial within patient design assessing the effect of 7.5 g of aromatics inunction (compared to a "no-treatment baseline" and to a petrolatum "placebo") on lung mucus clearance measured by a standard radioaerosol technique. RESULTS: Aromatic treatment significantly enhanced clearance at two time points 30 (p < 0.05) and 60 (p < 0.02) minutes postradioaerosol inhalation but had no demonstrable further effect over the following 5 hours despite further application of the inunction. The clearance improvement (relative to a baseline) observed during the first hour of testing was significantly correlated (p < 0.01) with the concentration level of aromatics. CONCLUSION: Our data, thus, provide objective evidence of a positive effect of aromatics inunction on mucus clearance in chronic airways obstruction.

Aged↗
PubMed1994

Functional imaging of effects of fragrances on the human brain after prolonged inhalation.

Beside olfactory or trigeminal stimulation of chemosensory receptor-cells some results in published literature suggest that fragrances show a direct affect on the brain. The effect of the fragrance 1,8-cineol, which was described in literature as 'stimulating', on regional and global cerebral blood flow (rCBF and gCBF) in the human brain after prolonged inhalation was investigated. The results show an increase of global-CBF without preference to primary or secondary olfactory centres after an inhalation-time of 20 min.

Adult↗
PubMed1995

Variation in odor thresholds for l-carvone and cineole and correlations with suprathreshold intensity ratings.

Specific anosmias have been reported for l-carvone and cineole, two compounds of importance in food flavor perception. Detection thresholds were assessed in groups of 50+ individuals by ascending forced-choice tests conducted in quadruplicate. Wide individual differences in thresholds were observed. Within the same session, threshold correlations were in the range of +0.8 to +0.9, showing good short-term reliability. Correlations with suprathreshold ratings were moderate (in the range of r = -0.5) after subtraction of false positive ratings for blank samples. However, a cineole mixture experiment failed to show any differences between subgroups that were previously classified as high or low sensitivity on the basis of threshold measurements. Re-testing selected groups after a period of months showed considerable within-individual variation in the thresholds, especially for l-carvone. These results call into question the stability and utility of threshold classification for these two compounds.

Adult↗
PubMed1995

Comparison of models of odor interaction.

Subjects rated the overall perceived intensity of concentrations of the odorants cineole, geraniol, hexyl salicylate, and linalyl acetate smelled alone and in binary mixtures. The subjects also rated intensity of specified constituents (e.g. amount of cineole in cineole, and in mixtures of cineole and linalyl acetate). The intensity of the stronger component alone offered a close description of perceived intensity. In addition to the Stronger Component model, two other psychological models (Vector and U model) and two psychophysical models (UPL2 and Equiratio Mixture model) offered descriptions ranging from fair to very good. Psychological models gave better fits, but lack explanatory power. Some results indicated that weaker odors add more potently than stronger odors, an outcome incompatible with these models. The psychophysical models, based on the additivity of single components, generally overestimated perceived intensity. Judgments of individual qualities gave only slight encouragement to any expectation of differences in masking or maskability among odorants. The results highlight the need to test particular critical hypotheses regarding how people perceive mixtures.

Acyclic Monoterpenes↗
PubMed1996

Pharmacokinetic studies of the fragrance compound 1,8-cineol in humans during inhalation.

The present study was undertaken to investigate the pharmacokinetics of 1,8-cineol in human subjects during prolonged inhalation. The results showed that 1,8-cineol is well absorbed from breathing air, with a peak plasma concentration after approximately 18 min. The elimination of this fragrance compound from the blood is biphasic, with a mean distribution half-life of 6.7 min and an elimination half-life of 104.6 min.

Administration, Inhalation↗
PubMed2000

'Microsmatic' primates revisited: olfactory sensitivity in the squirrel monkey.

Using a conditioning paradigm, the olfactory sensitivity of three squirrel monkeys to nine odorants representing different chemical classes as well as members of a homologous series of substances was investigated. The animals significantly discriminated dilutions as low as 1:10,000 n-propionic acid, 1:30,000 n-butanoic acid and n-pentanoic acid, 1:100,000 n-hexanoic acid, 1:1Mio n-heptanoic acid, 1:30, 000 1-pentanol, 1:300,000 1,8-cineole, 1:1Mio n-heptanal and 1:30Mio amyl acetate from the near-odorless solvent, with single individuals scoring even slightly better. The results showed (i) the squirrel monkey to have an unexpectedly high olfactory sensitivity, which for some substances matches or even is better than that of species such as the rat or the dog, and (ii) a significant negative correlation between perceptibility in terms of olfactory detection thresholds and carbon chain length of carboxylic acids. These findings support the assumptions that olfaction may play a significant and hitherto underestimated role in the regulation of primate behavior, and that the concept of primates as primarily visual and 'microsmatic' animals needs to be revised.

Aldehydes↗
PubMed2002

The C-terminal region of Escherichia coli UvrC contributes to the flexibility of the UvrABC nucleotide excision repair system.

Nucleotide excision repair in Escherichia coli involves formation of the UvrB-DNA complex and subsequent DNA incisions on either site of the damage by UvrC. In this paper, we studied the incision of substrates with different damages in varying sequence contexts. We show that there is not always a correlation between the incision efficiency and the stability of the UvrB-DNA complex. Both stable and unstable UvrB-DNA complexes can be efficiently incised. However some lesions that give rise to stable UvrB-DNA complexes do result in a very low incision. We present evidence that this poor incision is due to sterical hindrance of the damage itself. In its C-terminal region UvrC contains two helix-hairpin-helix (HhH) motifs. Mutational analysis shows that these motifs constitute one functional unit, probably folded as one structural unit; the (HhH)2 domain. This (HhH)2 domain was previously shown to be important for the 5' incision on a substrate containing a (cis-Pt).GG adduct, but not for 3' incision. Here we show that, mainly depending on the sequence context of the lesion, the (HhH)2 domain can be important for 3' and/or 5' incision. We propose that the (HhH)2 domain stabilises specific DNA structures required for the two incisions, thereby contributing to the flexibility of the UvrABC repair system.

Adenosine Triphosphatases↗
PubMed1997

Effects of components of Artemisia annua on coccidia infections in chickens.

Four experiments were run to test the anticoccidial activity of dried Artemisia annua leaves and several of their chemical constituents for possible use as prophylactic feed additives. When fed over a period of 3 wk at a level of 5%, a dried leaf supplement of A. annua provided significant protection against lesions due to Eimeria tenella but not Eimeria acervulina or Eimeria maxima. When fed over a period of 5 wk at a level of 1% to chicks undergoing immunization with a live vaccine, it provided significant protection in partially immunized chicks against E. acervulina and E. tenella lesions from a dual species challenge infection. It also afforded lower mean lesion scores in challenged chicks immunized over a period of 5 wk. Artemisinin, an antimalarial component of A. annua, was present at a level of 0.034% in the dried leaf preparation. A 5% supplement thus afforded about 17 ppm artemisin. When the pure compound was fed at that level for a period of 3 wk, it protected weight gains and significantly reduced lesion scores attributable to E. tenella but not E. acervulina. Other components of A. annua, camphor and 1,8-cineole, at 119 ppm also protected weight gains, and reduced E. tenella lesion scores. Camphor reduced E. acervulina lesions. Artemisinin fed for 4 wk at levels of 2, 8.5, and 17 ppm significantly reduced oocyst output from separate E. acervulina and E. tenella infections and a dual species infection. Pure artemisinin thus appears to be effective against at least two coccidia species when used as a feed additive, and its activity may depend, in part, on the length of time it is administered before a challenge infection.

Analysis of Variance↗
PubMed1991

Effects of a topically applied counterirritant (Eucalyptamint) on cutaneous blood flow and on skin and muscle temperatures. A placebo-controlled study.

This study was designed to investigate the effects of a new product of counterirritant, Eucalyptamint, on the cutaneous circulation and on skin and muscle temperatures. Ten normal subjects (six males and four females, with an average age of 34 +/- 6 yr) were involved in this study. Eucalyptamint was applied to the anterior forearm skin of one side, and placebo was applied to the contralateral forearm. The subjective feelings, cutaneous blood flow, and skin temperature were measured before and periodically (5-min intervals) after the application of the compound. Muscle temperature was measured before and 30 min after the application of the Eucalyptamint. There was no significant effect on the subjective sensation. However, there were statistically significant (P less than 0.05) increases in cutaneous blood flow (up to 4 times base-line) and skin temperatures (up to 0.8 degrees C higher than base-line) after the application of Eucalyptamint with the effects lasting up to 45 min after the application. The muscle temperature was also increased (0.4 degrees C) significantly (P less than 0.05) 30 min after application of the Eucalyptamint. There were no significant changes in the placebo application. The results of this study suggested that the new product of counterirritant, Eucalyptamint, produced significant physiologic responses that may be beneficial for pain relief and/or useful to athletes as a passive form of warm-up.

Adult↗
PubMedDate not supplied

Functional MRI of human olfaction.

PURPOSE: Our goal was to use functional MRI (fMRI) to measure brain activation in response to olfactory stimuli. METHOD: fMRI brain scans were obtained in 17 normal subjects (9 men, 8 women) using-multislice FLASH MRI in response to three olfactory stimuli (pyridine, menthone, amyl acetate) in three coronal brain sections selected from anterior to posterior temporal brain regions. Activation images were derived using correlation analysis, and ratios of areas of brain activated to total brain areas were calculated. RESULTS: Activation was present in each section in all subjects. Subjective estimation of vapor intensity followed relative vapor pressure of stimuli presented (pyridine > amyl acetate > menthone) and were similar for both men and women. However, brain activation did not follow subjective responsiveness order but rather pyridine > menthone > amyl acetate, a pattern demonstrated by both men and women. Brain activation in women was consistently lower than in men for all vapors in all brain sections, although regions of activation did not differ. Activation occurred in regions previously recognized as associated with olfactory stimulation, including orbitofrontal and entorhinal cortex; however, extensive regions within frontal cortex including cingulate gyrus were also activated. Brain regions activated to odors considered pleasant or unpleasant did not differ. CONCLUSION: The techniques used in this study demonstrated that brain activation to olfactory stimuli could be measured quantitatively such that differences between groups of subjects (in this case men and women) could be compared. Although localization of brain activation was not the major thrust of this study, activation to olfactory stimuli was found not only in brain regions previously associated with processing of olfactory information but also in several other areas of frontal cortex, in cingulate gyrus, and in several components of the limbic system. This is the first study in which activation in human brain parenchyma of normal humans to olfactory stimuli has been quantitated by fMRI.

Adult↗
PubMed1996

Modulation by cyclic GMP of the odour sensitivity of vertebrate olfactory receptor cells.

Recent evidence has indicated a significant role for the cGMP second messenger system in vertebrate olfactory transduction but no clear functions have been identified for cGMP so far. Here, we have examined the effects of 8-Br-cGMP and carbon monoxide (CO) on odour responses of salamander olfactory receptor neurons using perforated patch recordings. We report that 8-Br-cGMP strongly down-regulates the odour sensitivity of the cells, with a K1/2 of 460 nM. This adaptation-like effect can be mimicked by CO, an activator of soluble guanylyl cyclase, with a K1/2 of 1 microM. Sensitivity modulation is achieved through a regulatory chain of events in which cGMP stimulates a persistent background current due to the activation of cyclic nucleotide-gated channels. This in turn leads to sustained Ca2+ entry providing a negative feedback signal. One consequence of the Ca2+ entry is a shift to the right of the stimulus-response curve and a reduction in saturating odour currents. Together, these two effects can reduce the sensory generator current by up to twenty-fold. Thus, cGMP functions to control the gain of the G-protein coupled cAMP pathway. Another consequence of the action of cGMP is a marked prolongation of the odour response kinetics. The effects of CO/cGMP are long-lasting and can continue for minutes. Hence, we propose that cGMP helps to prevent saturation of the cell's response by adjusting the operational range of the cAMP cascade and contributes to olfactory adaptation by decreasing the sensitivity of olfactory receptor cells to repeated odour stimuli.

Ambystoma↗
PubMedDate not supplied

Optical recording of odor-evoked responses in the olfactory brain of the naïve and aversively trained terrestrial snails.

Regular spontaneous oscillations were recorded both electro- and optophysiologically using a voltage-sensitive absorption dye in the olfactory part of the brain (procerebral lobe of the cerebral ganglia) of the gastropod mollusk Helix lucorum. Odor application caused transient changes in procerebral oscillations, and an odor-evoked potential was recorded in the procerebrum (PC). The wave of evoked potential originated near the place of olfactory nerve entrance into the PC and propagated via the procerebral neuropile toward the cell body layer. The spread of the odor-evoked potential corresponded roughly to the neuropile area, whereas the spontaneous oscillations were recorded in the cell body layer of the PC and were not observed in the neuropile. Evoked potential did not produce additional events intercalated into the ongoing spontaneous oscillations. Changes in parameters of spontaneous oscillations to the repeated presentations of the same odor were variable. To estimate the role of spontaneous oscillations in odor encoding, we trained the snail to avoid cineole, using paired presentations of cineole and electric shock. Elaboration of conditioned aversion to cineole applications resulted in distinct pairing-specific changes in behavior of the snails and procerebral activity. Responses to odor (cineole) applications were not different in amplitude or frequency of spontaneous oscillations in control and trained snails, whereas ratio of amplitudes of the same oscillation wave in proximal and distal regions of the procerebrum was significantly different in control and aversively trained snails, reflecting changes in neural firing in certain areas of the olfactory lobe.

Animals↗
PubMed2000

Inhibition of plant asparagine synthetase by monoterpene cineoles.

Asparagine (Asn) synthetase (AS) is the key enzyme in Asn biosynthesis and plays an important role in nitrogen mobilization. Despite its important physiological function, little research has been done documenting inhibitors of plant AS. Plant growth inhibition caused by the natural monoterpene 1,4-cineole and its structurally related herbicide cinmethylin was reversed 65% and 55%, respectively, by providing 100 microM Asn exogenously. Reversion of the phytotoxic effect was dependent on the concentration of Asn. The presence of either 1,4-cineole or cinmethylin stimulated root uptake of [(14)C]Asn by lettuce (Lactuca sativa) seedlings. Although the physiological responses suggested that both compounds affected Asn biosynthesis, biochemical analysis of AS activity showed that the natural monoterpene was a potent inhibitor (I(50) = approximately 0. 5 microM) of the enzyme, whereas the commercial product was not inhibitory up to levels of 10 mM. Analysis of the putative metabolite, 2-hydroxy-1,4-cineole, showed that the cis-enantiomer was much more active than the trans-enantiomer, suggesting that the hydroxyl group was involved in the specific ligand/active site interaction. This is the first report that AS is a suitable herbicide target site, and that cinmethylin is apparently a proherbicide that requires metabolic bioactivation via cleavage of the benzyl-ether side chain.

Aspartate-Ammonia Ligase↗